Most patients achieve control with low dose of ICS, and in those who do not, only an additional 15-20% will have improved control with doubling of the dose
Onset of clinically significant effects
Symptoms improve in the first 1-2 weeks and will reach maximum improvement in 4-8 weeks
Lung function improvement begins in 1-2 weeks and usually plateaus at 4 weeks but may increase slightly thereafter for 6-8 weeks
Improvement in bronchial hyperresponsiveness requires 2-3 weeks and approaches maximum in 1-3 months but may continue to improve over 1 year
Maximum decrease in FeNO occurs within 1 week and returns to baseline levels within 1-2 weeks following discontinuation
Sensitivity to exercise challenge decreases after 4 weeks
Although the intensity of these responses can be dose dependent, the onset and offset of responses are not, nor do they differ significantly by which ICS is used
Symbicort SMART (Canada)
Single maintenance and reliever treatment, not US FDA approved
Instructions from Canadian package insert outlines 2 regimens adolescents/adults (12 and up):
Take 1 additional inhalation PRN if you feel symptoms. If symptoms persist after a few minutes, an additional inhalation should be taken. Not more than 6 inhalations should be taken on any single occasion.
The maximum recommended daily dose is 8 inhalations.
1-2 inhalations Symbicort 200 Turbuhaler BID or 2 inhalations QD
Take 1 additional inhalation PRN if you feel symptoms. If symptoms persist after a few minutes, an additional inhalation should be taken. Not more than 6 inhalations should be taken on any single occasion.
The maximum recommended daily dose is 8 inhalations.
Singulair (montelukast) - also approved for allergic rhinitis
Dosing
6 months-5 years - 4 mg oral granules packet PO QD
2-5 years - 4 mg chewable tablet PO QD
6-14 years - 5 mg chewable tablet PO QD
≥15 years - 10 mg tablet PO QD
≥15 years for EIB - 10 mg tablet at least 2 hours before exercise
Neuropsychiatric events have been reported, including agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, dream abnormalities, hallucinations, insomnia, irritability, restlessness, somnambulism, suicidal thinking and behavior (including suicide), and tremor
Limited data shows benefit in aspirin-sensitive asthma, and might benefit "neutrophilic asthma" due to blockade of LTB4
≥12 years - 1200 mg PO BID, within one hour after morning and evening meal
Contraindicated in active liver disease or persistent AST/ALT elevations ≥3x the upper limit of normal
Neuropsychiatric events have been reported
2-4% develop hepatotoxicity, usually within first 6 months of treatment. Obtain LFTs, every month x 3 months, every 2-3 months for the remainder of the first year, and periodically (e.g. 6 months per Phil Lieberman) thereafter.
ALT considered the most sensitive indicator of liver injury from zileuton
If signs of liver dysfunction develop or transaminase elevations ≥5x upper limit of normal occur, discontinue and follow AST/ALT until normal
Dry powder inhalers - except for Pulmicort Turbuhaler, all other DPIs (including Spiriva) available in the United States contain lactose which may be contaminated with cow's milk protein
Lactose intolerance and asthma medications - symptoms can occur if multiple lactose-containing medications are ingested. Lactose in DPIs is not likely an issue (Advair Diskus contains 12.5 mg lactose but 3 grams are needed to provoke symptoms, equivalent to amount found in 60 mL milk or 180 gram processed cheese).
Soy - CFC MDIs containing ipratropium (Atrovent CFC, Combivent) contain soy lecithin which may be contaminated with soy protein. New HFA forms of these inhalers and ipratropium nebulizer solutions do not contain soy lecithin.
MDI vs. Nebulizer
Administration of bronchodilator by MDI is 5-fold more efficient than delivery via nebulizer. (~2% of nebulized medication will reach the lungs compared with 10% an MDI dose).
The usual dose of albuterol delivered by nebulizer is 2.5 mg (2500 mcg) while 2 puffs from an MDI is 180 mcg. Using the above information, the dose delivered to the lung via nebulization would be 2% of 2500 mcg (50 mcg), compared with 10% of 180 mcg (18 mcg) delivered by MDI.
Thus, 2.5 mg albuterol via neb = ~5.5 puffs albuterol via MDI
Doses up to 20 puffs of albuterol is approximately equal to 2 mg oral albuterol
Sequence/timing of inhaled medications
There is no definitive evidence to indicate there is any advantage in using one type of inhaler before the other
It has been postulated that bronchodilators should be administered prior to ICS based on the rationale that bronchodilation would permit enhanced deposition of an ICS. However, bronchodilatation can take time and it is usually not achieved until 15-20 minutes after the inhalation of a SABA or formoterol and takes longer after salmeterol.
For most inhalers, 1-2 minutes between puffs is sufficient
For a bronchodilator, one might wish to wait 5-20 minutes to see if a second (or additional) inhalations are needed
Adrenal Suppression
Unlike other ICS medications, ciclesonide appears to have little or no suppressive effects on the HPA axis, and there is no evidence (and no case reports) of adrenal suppression with ciclesonide use
Table of Contents
Inhaled Corticosteroids
NAEPP
GINA 2012
(Not QVAR)
Clinical usage notes:
Symbicort SMART (Canada)
Anticholinergics
Leukotriene Modifiers
Anti-IgE
Related Controller Medication Issues
Asthma medications containing food allergens
MDI vs. Nebulizer
Sequence/timing of inhaled medications
Adrenal Suppression
References